The development of inhibitory alloantibodies to factor VIII is arguably one of the most severe and important complications of clotting factor concentrate exposure in haemophilia A. The development of an inhibitor compromises the ability to effectively manage haemorrhage, resulting in a greater rate of disability, complications and costs of therapy. This chapter briefly reviews the epidemiology, immunobiology, and laboratory evaluation of inhibitors. It discusses the therapeutic approach and management of inhibitors in various clinical settings and also focuses on inhibitor eradication practices (immune tolerance) and newer experimental strategies with potential clinical application for inhibitor prevention.